This application explores the metabolism of apoA-IV, a newly described human apoprotein. Both the liver and the intestine will be explored as sites of synthesis. The dietary factors which regulate its synthesis in the intestine will be explored by quantitating in intestinal biopsies by RIA apoA-IV levels after fat ingestion. The output of apoA-IV will be measured in chylous urine after the ingestion of different dietary lipids. ApoA-IV and other apoproteins will be localized within human liver biopsies using immunoperoxidase techniques. ApoA-IV exists in plasma mainly unassociated with the major lipoproteins, therefore apoA-IV in the d greater than 1.21g/ml fraction will be isolated and characterized. These studies will be performed using ultracentrifugation, immunoprecipitation, antibody affinity chromatography and incubation with Gabosil. In view of the established relationship between chylomicrons and HDL, HDL will be examined by density gradient ultracentrifugation and agarose column chromatography in normal subjects before and after the ingestion of cream. These studies will establish whether apoA-IV exists transiently in normal HDL. Preliminary studies in alcoholic hepatitis patients have demonstrated the presence of apoA-IV in plasma lipoproteins and especially in a discoid HDL particle which increased after the ingestion of lipid. Further lipid feeding studies are planned. Subjects will be fed fat and the presence of apoA-IV in HDL correlated with LCAT activity. Other subjects will be fed diets of different fat content and given cholestyramine in order to determine the role of the intestine in the production of the abnormal lipoproteins in alcoholic hepatitis. In vitro incubation studies will be performed in order to determine the fate of chylomicron apoA-IV and the factors which determine its final localization in plasma. These studies will provide information about the metabolism and the function of a recently described apoprotein. In addition, further information will be obtained as to the interrelationship between chylomicrons and HDL.